Laboratoire de Glycochimie, des Antimicrobiens
et des Agroressources UMR 7378 CNRS


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  • Tutelle UPJV

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Actualités et Publications

Mass Spectrometry, Ion Mobility Separation and Molecular Modelling: A Powerful Combination for the Structural Characterisation of Substituted Cyclodextrins Mixtures,

Rigaud, S.; Dosso, A.; Lesur, D.; Cailleu, D.; Mathiron, D.; Pilard, S.; Cezard, C.; Djedaini-Pilard, F.

Int J Mol Sci 2022, 23, 13352.

When working on the synthesis of substituted cyclodextrins (CDs), the main challenge remains the analysis of the reaction media content. Our objective in this study was to fully characterise a complex isomers mixture of Lipidyl-betaCDs (LipbetaCD) obtained with a degree of substitution 1 (DS = 1) from a one-step synthesis pathway. The benefit of tandem mass spectrometry (MS/MS) and ion mobility separation hyphenated with mass spectrometry (IM-MS) was investigated. The MS/MS fragment ion's relative intensities were analysed by principal component analysis (PCA) to discriminate isomers. The arrival time distribution (ATD) of each isomer was recorded using a travelling wave ion mobility (TWIM) cell allowing the determination of their respective experimental collision cross section (CCSexp). The comparison with the predicted theoretical CCS (CCSth) obtained from theoretical calculations propose a regioisomer assignment according to the betaCD hydroxyl position (2, 3, or 6) involved in the reaction. These results were validated by extensive NMR structural analyses of pure isomers combined with molecular dynamics simulations. This innovative approach seems to be a promising tool to elucidate complex isomer mixtures such as substituted cyclodextrin derivatives.

Copper-uptake mediated by an ecofriendly zwitterionic ionic liquid: A new challenge for a cleaner bioeconomy,

Vuillemin, M. E.; Waterlot, C.; Verdin, A.; Laclef, S.; Cézard, C.; Lesur, D.; Sarazin, C.; Courcot, D.; Hadad, C.; Husson, E.; Van Nhien, A. N.

Journal of Environmental Sciences 2022.

This study aims to investigate the ability of an imidazolium biobased Zwitterionic Ionic Liquids (ZILs) in enhancing the phytoavailability of copper from garden (G) and vineyard (V) soils using the model plant ryegrass. Uncontaminated and artificially contaminated CuSO4 soils, unamended and ZIL-amended soil modalities were designed. The copper/ZIL molar ratio (1/4) introduced was rationally established based on molecular modeling and on the maximal copper concentration in artificially contaminated soil. Higher accumulation of copper in the shoots was detected for the uncontaminated and copper contaminated ZIL amended V soils (18.9 and 23.3 mg.kg−1, respectively) contrary to G soils together with a ZIL concentration of around 3% w/w detected by LC-MS analyses. These data evidenced a Cu-accumulation improvement of 38 and 66% compared to non-amended V soils (13.6 and 13.9 mg.kg−1 respectively). ZIL would be mainly present under Cu(II)-ZIL4 complexes in the shoots. The impact on the chemical composition of shoot were also studied. The results show that depending on the soils modalitity, the presence of free copper and/or ZIL led to different chemical compositions in lignin and monomeric sugar contents. In the biorefinery context, performances of enzymatic hydrolysis of shoots were also related to the presence of both ZIL and copper under free or complex forms. Ecotoxicity assessment of the vineyard soil samples indicated that the quantity of copper and ZIL remaining in the soils had no significant toxicity. ZIL amendment in a copper-contaminated soil was demonstrated as being a promising way to promote the valorization of phytoremediation plants.

The formulation of a CMC binder/silicon composite anode for Li-ion batteries: from molecular effects of ball milling on polymer chains to consequences on electrochemical performances,

Ndour, M.; Bonnet, J.-P.; Cavalaglio, S.; Lombard, T.; Courty, M.; Aymard, L.; Przybylski, C.; Bonnet, V.

Materials Advances 2022.

The semi-synthetic polysaccharide carboxymethylcellulose (CMC) is one of the most studied and effective polymer binders for silicon-based anodes in Li-ion batteries. The formulation of the corresponding composite negative electrode with an appropriate mixture of electroactive silicon, a CMC binder and a carbon additive is mandatory to ensure a good electrical conductivity. Blending is commonly realized by a highly energetic ball milling treatment of these three aforementioned components. This type of mixing reduces the size of the obtained particles and can also potentially agglomerate them. Morever, it allows the formation of a nanostructured mixture which is essential for both the silicon activation and to achieve good electrochemical performance. However, such strong treatment can also cause a significant degradation of the polymer chains, as we have recently demonstrated for polyacrylic acid (PAA). In the present work, the structural and chemical effects of this mechanical grinding on three commercial CMCs ranging from 90 to 700 kg mol−1 were investigated. All the polymers were characterized using SEC-MALLS, FTIR spectroscopy, MALDI-TOF mass spectrometry and TGA-MS thermal analysis. In all cases, a huge average molecular weight decrease was noticed, leading to the appearance of a bimodal distribution with low (52–72 kg mol−1) to very low molecular weight populations (1–1.8 kg mol−1). From these results, two formulations of a negative electrode were compared, one with ball milling of the three compounds and another one including only ball milling steps for silicon and carbon. After the correlation of the characteristics of this negative electrode composite with the electrochemical results, it was demonstrated that a high number of functions for supramolecular or covalent linkages are keypoints of the herein anode performance. Low molecular weight CMC derivatives (about 64 kg mol−1) obtained by ball milling treatment led to higher stability of the electrode.

Tenure Track position at LG2A - Chaire de Professeur Junior au LG2A

The scientific project will be based on the synthesis of new glycosidic analogues for chemobiology in a general way, and more specifically for the study of sugar-protein interactions and/or the development of corresponding analytical tools and methodology. The project must be based on biosourced plateform molecules respecting the concepts of green/sustainable chemistry. For example, target compounds able to achieve selective inhibition of enzymes involved in carbohydrates biosynthesis or metabolism (glycosidases, glycosyltransferases). In this context, the project could involve the synthesis and biological evaluation of new inhibitors like S-, N-, or C-glycosidic analogues, in order to target bacterial enzymes or enzymes related to some diseases as the α-glucosidase (diabetes of type II) or heparanase (cancer metastasis). Proposals involving others aspects of glycochemistry and the study of sugar-protein interactions and supramolecular assemblies, or still methods of structural analysis, can also be envisaged.

Le projet scientifique reposera sur la synthèse d’analogues glycosidiques originaux dans le cadre de la chemobiologie de façon générale et plus spécifiquement pour l’étude des interactions sucre-protéine et/ou le développement des méthodes analytiques correspondantes. Le projet doit être basé sur des molécules plate-forme biosourcées respectant autant que possible les concepts de la chimie verte/durable. A titre d’exemple, on peut envisager des composés cibles capables d’inhiber sélectivement les enzymes impliquées dans la biosynthèse ou le métabolisme des glucides (glycosidases, glycosyltransferases). Dans ce cadre, le projet pourra impliquer la synthèse et l’évaluation biologique de nouveaux inhibiteurs de ces enzymes, comme par exemple des analogues S-, N-, ou C-glycosidiques, afin de cibler par exemple des enzymes bactériennes ou celles impliquées dans le développement de certaines maladies comme l’α-glucosidase (dans le diabète de type II) ou l’héparanase (dans la métastase de cancers). Des propositions concernant d’autres aspects de la glycochimie, ainsi que l’étude des interactions sucre-protéine et des assemblages supramoléculaires, ou encore des méthodes d’analyse structurale, seront également envisageables.

Sulfated Galactans from Gracilaria fisheri with Supplementation of Octanoyl Promote Wound Healing Activity In Vitro and In Vivo,

Rudtanatip, T.; Somintara, S.; Sakaew, W.; El-Abid, J.; Cano, M. E.; Jongsomchai, K.; Wongprasert, K.; Kovensky, J.

Macromol. Biosci. 2022, n/a, 2200172.

Abstract Sulfated galactans (SG) isolated from Gracilaria fisheri was partially degraded (DSG), and subsequentially supplemented with octanoyl (DSGO) and sulfate (DSGS) groups. The molecular weights of DSG, DSGO, and DSGS were 7.87, 152.79, and 97.07?kDa, respectively. The modification was confirmed using FTIR and NMR, whilst in vitro wound healing activity was assessed using scratched wound fibroblasts. The results revealed that DSGO exhibited highest percentage of wound closure in scratched fibroblast L929 cells. Furthermore, DSGO was able to promote proliferation and accelerate migration of scratched fibroblasts, which corresponded to the regulation of proteins and mRNA (Ki67, p-FAK, vimentin and E-cadherin) determined by Western blotting and qPCR analysis. The superior wound healing activity of DSGO was also confirmed in excision wound of rats. The results demonstrated that DSGO significantly enhanced the percentage of wound closure, re-epithelialization, and collagen arrangement, increased α-SMA and vimentin expression, and decreased that of TNF-α at the wound site. The results suggest that degraded SG supplemented with medium-chain fatty acids of octanoyl group might pass through the membrane, subsequently activating the mediators associated with proliferation and migration of fibroblasts, which could potentially lead to the promotion of wound healing activity. This article is protected by copyright. All rights reserved

Probing topology of supramolecular complexes between cyclodextrins and alkali metals by ion mobility-mass spectrometry,

Przybylski, C.; Bonnet, V.

Carbohydr. Polym. 2022, 297, 120019.

In this study, the size and shape of supramolecular assemblies between cyclo-oligosaccharides and proton, ammonium or a series of alkali metals by electrospray coupled to trapped ion mobility-mass spectrometry (ESI-TIMS) have investigated. Native cyclodextrins (CD) were selected as models, and collision cross section (CCS) values were deducted for the main positive singly and doubly charged species. Experimental CCS values were in good agreement with those obtained from molecular modeling. Due to the high mobility resolving power and resolution, it was possible to highlight the presence of various conformers. Also, TIMS allowed to discriminate and estimate the content of various orientations from non-covalent nanotubes-based CD, involving secondary/secondary rim hydroxyl groups (head-to head), primary/secondary rim (head-to-tail) hydroxyl groups or primary/primary rim (tail-to-tail) hydroxyl groups interactions. Such results pave the way for a better knowledge of the topology of cyclo-oligosaccharides based supramolecular complexes, demonstrating that TIMS can be a particularly attractive molecular descriptor.

Mechanochemical synthesis of (4S)-N-alkyl-4,5-bis-sulfooxypentanamide via a one-pot sequential aminolysis-sulfation reaction of (S)-γ-hydroxymethyl-γ-butyrolactone (2H-HBO),

Herrlé, C.; Toumieux, S.; Araujo, M.; Peru, A.; Allais, F.; Wadouachi, A.

Green Chem. 2022.

To valorize further the highly valuable bio-based platform (S)-γ-hydroxymethyl-γ-butyrolactone (2H-HBO), whose sustainable kiloscale-synthesis from cellulose-derived levoglucosenone (LGO) has been validated, a mechanochemical strategy was developed to produce new potential bio-based surfactants under solventless conditions. First, the reaction of 2H-HBO with primary or secondary amines was investigated followed by a sulfation reaction with the isolated N-alkyl-amide derivatives to obtain the corresponding N-alkyl sulfated compounds. The latter was then obtained by an optimized one-pot sequential aminolysis–sulfation in a planetary ball mill with excellent efficiency. For the first time, sulfated compounds arising from bio-based/renewable resources were obtained exclusively via a mechanochemical process. As a result, the sulfated derivatives of 2H-HBO were formed quantitatively and isolated in 69–79% overall yields. The critical micelle concentration (CMC) was determined for some of them which exhibited interesting anionic surfactant properties.

Recent Advances in the Synthesis of Five-Membered Cyclic Carbonates and Carbamates from Allylic or Propargylic Substrates and CO2,

Vranješević, F.; Kolympadi Markovic, M.; Matulja, D.; Ambrožić, G.; Sordo, J. Á.; Laclef, S.; Vrček, V.; Marković, D.

Catalysts 2022, 12, 547.

The organic carbamates and carbonates are highly desirable compounds that have found a wide range of applications in drug design, medicinal chemistry, material science, and the polymer industry. The development of new catalytic carbonate and carbamate forming reactions, which employ carbon dioxide as a cheap, green, abundant, and easily available reagent, would thus represent an ideal substitution for existing methods. In this review, the advancements in the catalytic conversion of allylic and propargylic alcohols and amines to corresponding five-membered cyclic carbonates and carbamates are summarized. Both the metal- and the organocatalyzed methods are reviewed, as well as the proposed mechanisms and key intermediates of the illustrated carbonate and carbamate forming reactions.

Using NMR to Dissect the Chemical Space and O-Sulfation Effects within the O- and S-Glycoside Analogues of Heparan Sulfate,

Meneghetti, M. C. Z.; Naughton, L.; O’Shea, C.; Koffi Teki, D. S. E.; Chagnault, V.; Nader, H. B.; Rudd, T. R.; Yates, E. A.; Kovensky, J.; Miller, G. J.; Lima, M. A.

ACS Omega 2022.

Heparan sulfate (HS), a sulfated linear carbohydrate that decorates the cell surface and extracellular matrix, is ubiquitously distributed throughout the animal kingdom and represents a key regulator of biological processes and a largely untapped reservoir of potential therapeutic targets. The temporal and spatial variations in the HS structure underpin the concept of “heparanome” and a complex network of HS binding proteins. However, despite its widespread biological roles, the determination of direct structure-to-function correlations is impaired by HS chemical heterogeneity. Attempts to correlate substitution patterns (mostly at the level of sulfation) with a given biological activity have been made. Nonetheless, these do not generally consider higher-level conformational effects at the carbohydrate level. Here, the use of NMR chemical shift analysis, NOEs, and spin–spin coupling constants sheds new light on how different sulfation patterns affect the polysaccharide backbone geometry. Furthermore, the substitution of native O-glycosidic linkages to hydrolytically more stable S-glycosidic forms leads to observable conformational changes in model saccharides, suggesting that alternative chemical spaces can be accessed and explored using such mimetics. Employing a series of systematically modified heparin oligosaccharides (as a proxy for HS) and chemically synthesized O- and S-glycoside analogues, the chemical space occupied by such compounds is explored and described.

Fast and Efficient Mechanosynthesis of Aldonamides by Aminolysis of Unprotected Sugar Lactones,

Bil, A.; Abdellahi, B.; Pourceau, G.; Wadouachi, A.

Sustainable Chemistry 2022, 3, 300-311.

Sugar amides, such as aldonamides, are interesting, sugar-based molecules used in various fields, from detergency to medicine. Nevertheless, their valorization, especially as alternatives to petroleum-based substances, can be slowed down by their synthetic pathway, which is generally not in accordance with green chemistry principles, and is also not economically competitive. We propose herein a fast procedure for the synthesis of aldonamide-derived glycoconjugates with mechanochemistry. The conditions were first optimized with galactonolactone, used as a model lactone, and dodecylamine. After only 5 min of grinding of stoechiometric amounts of amine and lactone, in the presence of water used as a Liquid Assisted Grinding (LAG) agent, the corresponding galactonamide was isolated with a high yield (90%) after a simple aqueous work-up. The optimized conditions were then applied to a wide variety of amines and sugar lactones, showing the versatility of the methodology. Gluco- and ribono-lactone exhibited similarly excellent reactivity, showing that the procedure is not sugar-dependent. Furthermore, the procedure was shown to be compatible with various functional groups such as alkene, alkyne, thiol, ester and hydroxyl.

Laboratoire de Glycochimie, des Antimicrobiens et des Agroressources
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